rs2048716

Variant names:

• chr17-66527875-G-A
• rs2048716
• NM_002737.3:c.288+31592G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002737.3(PRKCA):​c.288+31592G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,014 control chromosomes in the GnomAD database, including 6,087 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (6087 hom., cov: 32)
• Consequence: PRKCA NM_002737.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.182
• Publications: 5 publications found

Genes affected

PRKCA (HGNC:9393): (protein kinase C alpha) Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role in cells. The protein encoded by this gene is one of the PKC family members. This kinase has been reported to play roles in many different cellular processes, such as cell adhesion, cell transformation, cell cycle checkpoint, and cell volume control. Knockout studies in mice suggest that this kinase may be a fundamental regulator of cardiac contractility and Ca(2+) handling in myocytes. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKCA	NM_002737.3	c.288+31592G>A		intron_variant	Intron 3 of 16	ENST00000413366.8	NP_002728.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKCA	ENST00000413366.8	c.288+31592G>A		intron_variant	Intron 3 of 16	1	NM_002737.3	ENSP00000408695.3
PRKCA	ENST00000578063.5	n.288+31592G>A		intron_variant	Intron 3 of 9	1		ENSP00000462087.1
PRKCA	ENST00000284384.6	n.280-26644G>A		intron_variant	Intron 3 of 14	5		ENSP00000284384.6

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38601 AN: 151898 Hom.: 6068 Cov.: 32

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.261

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.254 AC: 38671 AN: 152014 Hom.: 6087 Cov.: 32 AF XY: 0.255 AC XY: 18924 AN XY: 74286

African (AFR) AF: 0.428 AC: 17741 AN: 41452

American (AMR) AF: 0.294 AC: 4489 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.240 AC: 833 AN: 3470

East Asian (EAS) AF: 0.300 AC: 1550 AN: 5174

South Asian (SAS) AF: 0.144 AC: 693 AN: 4812

European-Finnish (FIN) AF: 0.186 AC: 1954 AN: 10528

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10628 AN: 67992

Other (OTH) AF: 0.261 AC: 551 AN: 2108

Alfa AF: 0.222 Hom.: 603

Bravo AF: 0.272

Asia WGS AF: 0.236 AC: 820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.4
DANN	Benign	0.76
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2048716; hg19: chr17-64523993;